Comparative Effectiveness and Cost Effectiveness of a Multitarget Stool DNA Test to Screen for Colorectal Neoplasia.

We developed a model to determine whether a multitarget stool DNA (MT-sDNA) test that detects colorectal cancer (CRC) and polyps with higher sensitivity and lower specificity, but at a higher cost, than the fecal immunochemical test (FIT) can be used in screening. We used a Markov model of average-risk CRC screening to compare the effectiveness and cost effectiveness of screening with the MT-sDNA test vs FIT or colonoscopy. We accounted for the complex longitudinal participation patterns observed in organized programs vs opportunistic screening, as well as organized programs' patient support costs and differential payment rates by commercial insurers vs Medicare. With optimal adherence, yearly FIT and colonoscopy every 10 years were dominant (more effective and less costly) than MT-sDNA every 3 years. Compared with successful organized FIT programs (50% consistent and 27% intermittent participation; patient support costs, $153/cycle), the patient support program for the MT-sDNA test would need 68% of subjects to participate consistently and 32% to participate intermittently every 3 years, or the MT-sDNA test would need to cost 60% less than in the base case ($260 commercial payment and $197 Medicare payment), for the MT-sDNA test to be preferred over FIT at a threshold of $100,000 per quality-adjusted life-year (QALY) gained. Compared with opportunistic yearly FIT screening (15% consistent and 30% intermittent participation), performing the MT-sDNA test every 3 years would cost less than $100,000 per QALY gained if the MT-sDNA test achieved a participation rate more than 1.7-fold that of FIT. The results were robust in sensitivity analyses. Assuming equal participation across strategies and a threshold of $100,000 per QALY gained, FIT was preferred in 99.3% of iterations in Monte Carlo simulation. In a Markov model, we found FIT and colonoscopy to be more effective and less costly than the MT-sDNA test when participation rates were equal for all strategies. For the MT-sDNA test to be cost effective, the patient support program included in its cost would need to achieve substantially higher participation rates than those of FIT, whether in organized programs or under the opportunistic screening setting that is more common in the United States than in the rest of the world.

Ladabaum U ，Mannalithara A 《-》

Cost-Effectiveness of Multitarget Stool DNA Testing vs Colonoscopy or Fecal Immunochemical Testing for Colorectal Cancer Screening in Alaska Native People.

To estimate the cost-effectiveness of multitarget stool DNA testing (MT-sDNA) compared with colonoscopy and fecal immunochemical testing (FIT) for Alaska Native adults. A Markov model was used to evaluate the 3 screening test effects over 40 years. Outcomes included colorectal cancer (CRC) incidence and mortality, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The study incorporated updated evidence on screening test performance and adherence and was conducted from December 15, 2016, through November 6, 2019. With perfect adherence, CRC incidence was reduced by 52% (95% CI, 46% to 56%) using colonoscopy, 61% (95% CI, 57% to 64%) using annual FIT, and 66% (95% CI, 63% to 68%) using MT-sDNA. Compared with no screening, perfect adherence screening extends life by 0.15, 0.17, and 0.19 QALYs per person with colonoscopy, FIT, and MT-sDNA, respectively. Colonoscopy is the most expensive strategy: approximately $110 million more than MT-sDNA and $127 million more than FIT. With imperfect adherence (best case), MT-sDNA resulted in 0.12 QALYs per person vs 0.05 and 0.06 QALYs per person by FIT and colonoscopy, respectively. Probabilistic sensitivity analyses supported the base-case analysis. Under varied adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs, $1740-$75,868 per QALY saved) compared with FIT and colonoscopy. Each strategy reduced costs and increased QALYs compared with no screening. Screening by MT-sDNA results in the largest QALY savings. In Markov model analysis, screening by MT-sDNA in the Alaska Native population was cost-effective compared with screening by colonoscopy and FIT for a wide range of adherence scenarios.

Redwood DG ，Dinh TA ，Kisiel JB ，Borah BJ ，Moriarty JP ，Provost EM ，Sacco FD ，Tiesinga JJ ，Ahlquist DA ... -  《-》

Analysis of the effectiveness of two noninvasive fecal tests used to screen for colorectal cancer in average-risk adults.

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Although a significant proportion of CRC cases and deaths are preventable by screening, the morbidity and mortality from CRC remains high and is attributed to suboptimal screening rates. Low levels of population CRC screening uptake may be due to reluctance toward invasiveness of some screening tests, embarrassment, exposure to anesthesia, and grueling preparation, especially for the invasive screening tests. Noninvasive tests overcome many of these barriers because they are more convenient and potentially more attractive to patients compared to invasive tests. This study uses Markov cohort simulation model developed with the help of TreeAge pro software to compare two noninvasive fecal CRC screens, fecal immunohistochemical test (FIT) and multitarget stool DNA test (Mt-sDNA) with no screening in order to identify the more effective noninvasive fecal test to screen for colorectal cancer in average-risk adults. Simulation study developed with Markov model using TreeAge pro software, which included a hypothetical cohort at the average risk of developing colorectal cancer. Markov model was used to compare population-level CRC-related cases and deaths averted, life-years gained (LYG), and colonoscopies required for two noninvasive CRC screening strategies compared with no screening: annual fecal immunohistochemical testing (FIT) and 3-yearly multitarget stool DNA testing (Mt-sDNA). The model simulated the natural history of the adenoma-carcinoma sequence in average-risk persons starting at age 50 years, and natural history parameters were estimated from the literature and via verification to data on precancerous lesions (i.e. adenomas) and CRC incidence. Screening strategies were then superimposed on the natural history component of the model, allowing for precancerous lesions to be detected and removed, or CRC to be detected and treated at a potentially earlier stage. The sensitivity and specificity for each screen for precancerous lesions and CRC were the performance parameters used to estimate the effectiveness. Annual FIT was more effective than three yearly Mt-sDNA in reducing CRC cases, averting CRC-related deaths, and increasing the LYG compared to no screening. On average, annual FIT resulted in 3.5 fewer CRC cases, and 2.9 fewer CRC deaths per 1000 persons screened compared to 3-yearly Mt-sDNA. Annual FIT usage resulted in a 0.18 LYG compared to Mt-sDNA, which allowed 0.16 LYG, and an annual FIT screening led to a total of 203 more colonoscopies performed compared to Mt-sDNA. One-way sensitivity analysis conducted over the sensitivity rates of each screen by type of lesion showed that FIT remained the more effective strategy for all ranges of sensitivity. Threshold analysis results identified the lowest FIT sensitivity value at which Mt-sDNA performed better for conventional high-risk adenomas and CRC detection to be 0.16 and 0.052, respectively. Both the noninvasive screens were effective compared to no screening. Additionally, annual FIT as a first step noninvasive screening test for CRC appears to be more effective compared to three-yearly Mt-sDNA.

Sharma T 《-》

Screening for Colorectal Cancer Using a Multitarget Stool DNA Test: Modeling the Effect of the Intertest Interval on Clinical Effectiveness.

A multitarget stool DNA (mt-sDNA) test was recently approved for colorectal cancer (CRC) screening for men and women, aged ≥ 50 years, at average risk of CRC. The guidelines currently recommend a 3-year interval for mt-sDNA testing in the absence of empirical data. We used clinical effectiveness modeling to project decreases in CRC incidence and related mortality associated with mt-sDNA screening to help inform interval setting. The Archimedes model (Archimedes Inc., San Francisco, CA) was used to conduct a 5-arm, virtual, clinical screening study of a population of 200,000 virtual individuals to compare the clinical effectiveness of mt-sDNA screening at 1-, 3-, and 5-year intervals compared with colonoscopy at 10-year intervals and no screening for a 30-year period. The study endpoints were the decrease in CRC incidence and related mortality of each strategy versus no screening. Cost-effectiveness ratios (US dollars per quality-adjusted life year [QALY]) of mt-sDNA intervals were calculated versus no screening. Compared with 10-year colonoscopy, annual mt-sDNA testing produced similar reductions in CRC incidence (65% vs. 63%) and related mortality (73% vs. 72%). mt-sDNA testing at 3-year intervals reduced the CRC incidence by 57% and CRC mortality by 67%, and mt-sDNA testing at 5-year intervals reduced the CRC incidence by 52% and CRC mortality by 62%. At an average price of $600 per test, the annual, 3-year, and 5-year mt-sDNA screening costs would be $20,178, $11,313, and $7388 per QALY, respectively, compared with no screening. These data suggest that screening every 3 years using a multitarget mt-sDNA test provides reasonable performance at acceptable cost.

Berger BM ，Schroy PC 3rd ，Dinh TA 《-》

Multitarget stool DNA tests increases colorectal cancer screening among previously noncompliant Medicare patients.

Prince M ，Lester L ，Chiniwala R ，Berger B ... -  《-》